Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type I interferon signaling by targeting STAT1
Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type I interferon signaling by targeting STAT1
复制标题
蓝舌病毒非结构蛋白 3 (NS3) 和 NS4 通过靶向 STAT1 协同拮抗Ⅹ型干扰素信号传导
DOI：
10.1016/j.vetmic.2021.108986
复制
发表时间：
2021-01-22
影响因子：
3.3
通讯作者：
Li, Huachun
中科院分区：
文献类型：
--
作者：
Li, Zhuoran;Lu, Danfeng;Li, Huachun
已有研究指出，蓝舌病病毒（BTV）通过靶向Janus酪氨酸激酶（JAK）-信号转导和转录激活蛋白（STAT）通路，下调I型干扰素（IFN-I）的表达水平，抑制IFN-I信号转导。然而，单个病毒蛋白不能有效地阻断IFN-I信号传导。BTV病毒蛋白协同拮抗IFN-1信号转导的机制有待进一步研究。我们研究了BTV-1非结构蛋白3（NS 3）和NS 4通过直接与STAT 1相互作用来抵消JAK-STAT通路中IFN-I信号传导的协调作用。NS 3和NS 4靶向STAT 1的SH 2结构域，以抑制其磷酸化、异源二聚化、核转位以及JAK-STAT通路下游基因的激活。NS 3和NS 4以剂量依赖性方式损害IFN-1诱导的STAT 1磷酸化。总之，本研究证实BTV的NS 3和NS 4参与干扰IFN-I信号传导过程。此外，还揭示了BTV逃避宿主先天免疫反应的新机制。
Previous studies have pointed out that bluetongue virus (BTV) down-regulates the expression levels of type I interferon (IFN-I) and inhibits IFN-I signaling by targeting on the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription protein (STAT) pathway. However, individual viral protein could not effectively block IFN-I signaling. There is a need to explore the underlying mechanisms by which viral proteins of BTV coordinate to antagonize the IFN-I signaling. We investigated the coordinative role of BTV-1 nonstructural protein 3 (NS3) and NS4 in counteracting IFN-I signaling in the JAK-STAT pathway by directly interacting with STAT1. The NS3 and NS4 targeted the SH2 domain of STAT1 to inhibit its phosphorylation, heterodimerization, nuclear translocation, as well as activation of downstream genes of the JAK-STAT pathway. NS3 and NS4 impaired STAT1 phosphorylation induced by IFN-I in a dose dependent manner. Overall, this study confirmed that NS3 and NS4 of BTV participate in interfering with IFN-I signaling process. Also, a new mechanism employed by BTV to evade host innate immune responses was revealed.